Radiologists play god at their own risk
ene manipulation continues to grow as a topic for discussion. The argument that radiologists are not professionally affected by this issue and so should not get involved with the debate is misguided. Radiology is moving increasingly into therapeutic medicine, the latest step being the inclusion of radiologists in gene therapy teams. Gene therapy will eventually correct genetic deficiencies, such as severe combined immunodeficiency cystic fibrosis, and treat a variety of malignant diseases, including oncologic and chronic pathological processes like peripheral arterial ischemia. Nobel Prizes have already been awarded for this sort of research.
Two excellent reviews of gene therapy, one of which includes a glossary, have been published in RadioGraphics [1,2]. Both articles provide insight into this exciting new medical and radiological field, and they stress the crucial role for radiologists in diagnostics and therapeutics.
"Molecular imaging links diagnostic radiology to gene therapy."
Diagnostic radiology is moving toward molecular imaging. New techniques are being developed to image genetic manipulations, to perform in vivo screening of novel drugs, and to understand functional molecular events in living organisms at cellular and molecular levels . Everybody seems to have an opinion concerning gene manipulation and gene therapy, but hardly anybody has any solid information. The implications of gene technology will be tremendous, and radiologists will be the accomplices of those who have developed the altered genes for gene therapy, whether the outcome is positive or negative.
Gene therapy and molecular imaging are only the latest in the explosion of new technologies in therapeutic and diagnostic medicine that emerged during the last century.
One major contribution was the discovery and development of antibiotics in the fight against infectious diseases.
I learned to use antibiotics carefully in medical school. Try to identify the bacterium and test its susceptibility against antibiotics before you choose one and start therapy, I was told. It was considered the medical equivalent of a cardinal sin to prescribe an inappropriate antibiotic or to provide a course of antibiotics that lasted less than 10 days (even if the symptoms of the disease had disappeared).
Times have changed. Manufacturers of antibiotics now produce drugs by the ton and sell them as animal fodder to overcome inadequate diet and imperfect management practices in animal breeding. The cost of using antibiotics in healthy animals is said to be 60 euros per sow on a small farm; if production is concentrated at big farms, the cost may exceed 150 euros per animal. Many farmers are unaware that antibiotics are part of the fodder they give to their animals. Restrictions on the use of antibiotics in humans still exist, but the limits we learned at medical school do not apply to cows and pigs. The danger of creating the resistant bacteria that we were warned about is of no concern in animals. Increasingly, however, there are reports that resistance to antibiotics creates havoc in the treatment of infectious diseases.
The connection to radiology is not obvious, but this is just the first reminder of how things can go wrong when economic advantage allows some people to take action for which the rest of humankind later has to pay the price. Infectious diseases and resistant bacterial strains are on the increase. Just ask your colleagues in internal medicine.
Nuclear medicine and radiation therapy are twins of gene manipulation medicine. Diagnosis and treatment with radioactive isotopes grew out of research into nuclear arms and nuclear power. Nuclear science has contributed substantially to diagnosis and treatment of patients and to the understanding of metabolic processes.
Compared to gene manipulation, nuclear science can be controlled easily. Gene manipulation cannot be controlled because access to the technology will be simple. While you will be able to manipulate genes in your garage, building a hydrogen bomb is more difficult. Gene manipulation and its associated medicine will have a similar outcome to technology and medicine: major advances in the treatment of a number of diseases, but also be terrible accidents of a magnitude that we cannot imagine. Genetic manipulation is the ultimate tool with the ultimate risk.
What can go wrong? Numerous unforeseen outcomes have to be considered. Examples in agriculture already exist. One known possibility is unwanted gene transfer. Antibiotic-resistant maize (corn), for instance, already exists. The genes from this strain of maize can be taken up by bacteria in the human gastrointestinal tract and incorporated into human genes, making the unwitting recipient resistant to antibiotics.
As the Chinese proverb says: "Who rides a tiger cannot dismount any more." Or, in the language of a common U.S. dictum: "If anything can go wrong, it will" (Murphy's Law).
Companies involved in the development and use of genetically manipulated plants and animals stress that there are no hazards, yet they fight any legislation that would make developers and vendors responsible and liable for their products and any side effects they may cause, even years after initial introduction. Perhaps this is a sign of insecurity. Given the strong interrelationship between the drug companies and the politicians in charge, they will doubtless avoid the consequences.
Another Chinese proverb accounts for the companies' standpoint: "Who can tie a bell around the tiger's neck is also able to untie it." But there is a third Chinese proverb: "Whether you hurry or walk slow, the way in front of you stays the same." There is no hurry in genetic engineering.
Learning from mistakes
People seem reluctant to learn from mistakes. Greed has become a major factor of our lives, and businesspeople and politicians control medicine. Despite a deep mistrust in the decision-making process, demands that gene manipulation be discontinued are naive.
Daily vigilance and discussion are the only way to steer free of the extremes. Historical experience is a constant reminder that we should never take peace, freedom, and democracy for granted. It is up to us to help supervise this system so that it does not get out of control. Too many influential groups put their own well-being, money, and power first. State and supranational bureaucracies will not react in time, nor will they function properly, if lobbies are in pursuit.
One of the arguments in favor of gene manipulation is the historical nature of cross-fertilization experiments; e.g., Gregor Mendel and his studies on pea plants. Most of these early studies were carried out on plants, but a few experiments were performed on animals, too. Those pigs with additional ribs are excellent for barbecues.
Today we can perform such experiments in a more sophisticated "scientific" manner, or what we believe is scientific. We could eliminate inborn diseases, reducing the need for euthanasia and abortion. We could also eliminate certain race-specific features, or even entire races. Where do we draw the line? Somebody has to decide, sooner or later. Never before in medical history have the stakes been higher.
Farmers will be blamed if something goes wrong in agriculture. In medicine, it will be the doctors – not the politicians.
On the other hand, I am looking forward to the genetically engineered radiologist with four eyes, who can see like an eagle. This futuristic person might help me find the envelope containing x-rays that I put aside yesterday to show to a colleague. Where is it?
1. Voss SD, Kruskal JB. Gene therapy: a primer for radiologists. RadioGraphics 1998; 18: 1343-1372.
2. Thomas JW, Kuo MD, Chawla M, et al. Vascular gene therapy. RadioGraphics 1998; 18: 1373-1394.
3. Weissleder R. Molecular imaging: exploring the next frontier. Radiology 1999; 212: 609-614